ABSTRACT: By 2030, older adults will outnumber children with 25% of the population of the United States age 65 or older. The rate of Alzheimer?s disease (AD) and related dementias will also increase as the size and proportion of the older adult population continues to expand. In the past decade, deaths from AD have increased more than 120% in the US and AD is currently a leading cause of death. The impact on public health systems from increased care for those with declining medical and mental health is a major concern. An additional important concern is for the quality of life in older adults who are aging typically but experiencing decline in memory and cognitive function. Mild cognitive impairment (MCI) can begin in middle age and increase throughout the lifespan affecting many aspects of daily function. To date there is no effective cure or treatment to slow progression of MCI or AD. Prevention, however, is a growing possibility with some recent evidence that enhancement of cognitive function may reduce effects and delay the onset of MCI, AD and related dementias. One of the more promising current approaches to enhancing cognitive performance is use of video-games. Action video games can improve selective attention, processing speed and working memory. Advantages of game-based cognitive training include the ease of use at home which provides for extended distributed practice and high engagement. We propose a project that uses video-games for cognitive enhancement that differ critically from those currently in use. Our training games use gaze to train attention which forces a constant high level of engagement. Additionally, these games target specific attentional skills that are affected in typical aging (distraction and response inhibition) and that affect executive and memory function as well as practical function such as driving safety. These games have been used successfully to train impaired attention including resistance to distraction in teens and young adults with developmental disorders. We expect training to be equally effective in older adults. We propose to use the 2-year planning period to conduct a clinical trial that aims: to identify and address any modifications of the games required for adaptation to diminished sensory abilities in older adults; to optimize training dosage and test timing of retention of effects; and to test and refine the battery of outcome assessments. A subsequent large sample randomized control trial of healthy adults aged 60-80 would employ: 4 participant groups (active trainees, 2 active control groups, a group with MCI); 4 levels of outcome assessment (1. primary measures of attention; 2. EEG, FMRI, structural and DTI biomarkers of change (with a focus on brain regions vulnerable in AD such as hippocampus, medial temporal lobe); 3. assessment of cognitive/memory function; and 4. assessment of practical function and perception of self-efficacy). A long-term follow-up would assess the rate of MCI, AD and related dementias in trained compared to control samples. Our cross-disciplinary leadership team represents expertise in AD/MCI research, neuropsychology, geriatric mental health, clinical trial methods, biostatistics and development and use of games for health-related assessment and intervention.